POS0053 EARLY DIAGNOSIS, PROMPT INITIATION OF METHOTREXATE AND TREATMENT STEERED-TO-TARGET DO NOT ABROGATE THE RISK OF BEING MULTIDRUG REFRACTORY FOR PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: B. D’onofrio, V. Morandi, F. Maggiore, M. DI Lernia, L. De Stefano, C. Montecucco, S. Bugatti
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The management of rheumatoid arthritis (RA) has substantially improved during the last few decades; despite that, a significant proportion of patients remain refractory to conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), as well as to one or more biologic/target-synthetic (b/ts) DMARDs. It is estimated the overall proportion of refractory RA is around 3-17%. Refractory disease has been defined among patients with established, long-standing, RA. However, at present time, it is not known whether early diagnosis, prompt institution of DMARD within the window of opportunity and treatment steered-to-target are efficacious to prevent multidrug failure in patients with new-diagnosed RA. <h3>Objectives</h3> First, to assess if an Early Arthritis Clinic (EAC) background – early diagnosis and treatment within the "window of opportunity", disease management according to treat-to-target (T2) strategy – reduces the risk of being DMARDs refractory; secondly, to detect possible predictors of refractoriness in patients escalated to b/tsDMARDs. <h3>Methods</h3> Data were retrieved from a prospective monocentric cohort of 810 patients with early RA (symptoms duration &lt;12 months at inclusion) diagnosed between 2005-2017 and treated with csDMARDs (methotrexate in 90.4% of the cases) according to a T2T strategy in the setting of an EAC. The population of interest included all patients escalated to b/tsDMARDs because of inefficacy/intolerance to csDMARDs. The frequency and factors associated with failure to first and second b/tsDMARDs were analysed by logistic regression. <h3>Results</h3> A total of 135/816 (16.5%) early RA patients required treatment escalation to a b/tsDMARDs after a median (IQR) of 18.5 (11-39) months from diagnosis; of them, 117 had follow-up visits available for a median (IQR) of 96 (37-122.5) months after treatment initiation. Fifty-six patients (50.4%) failed the first b/tsDMARD after a median (IQR) of 14 (7.3-44.3) months due to inefficacy/side effects. The rates of failure of the second and third b/tsDMARD were 20.5% and 19.7%. Thirteen patients (11.1%) could be defined D2T, having failed a median (IQR) number of 2 (2-3) b/tsDMARDs with different mechanisms of action, and 3 (2.8-4) different b/tsDMARDs in general. By logistic regression, significant predictors of first b/tsDMARD failure were disease duration ≤24 months and autoantibody-negativity (respectively HR 1.89, 1.01-4.12, p=0.03; HR 1.66, 1.00-3.15, p=0.04). The latter confirms to be a significant predictor of second b/tsDMARD failure as well (HR 2.13, 1.08-4.17, p=0.03). At univariable analysis, significant predictors of D2T were concomitant diagnosis of fibromyalgia, autoantibody-negative status and lower doses of methotrexate. At bivariate logistic regression, fibromyalgia and autoantibody-negative RA maintained independent association with adjusted ORs (95% CI) of 3.6 (1.02-16.4) and 4.3 (1.01-24.1), respectively. <h3>Conclusion</h3> Early diagnosis, prompt initiation of methotrexate and management according to T2T strategy have substantially improved RA outcomes, and only about 16% of patients require escalation to second-line therapies. However, in those refractory to csDMARD, EAC setting seems not to ameliorate treatment persistence, as retention rates of b/tsDMARDs are similar to those observed in established disease. Early methotrexate inefficacy and autoantibody-negative disease appear to be predictive of first b/tsDMARD failure; moreover, patients with autoantibody-negative disease maintain a higher risk of failure of subsequent lines of therapies. Collectively, our findings suggest the need for a more tailored approach to refractory RA patients, especially to autoantibody-negative ones. <h3>Reference</h3> [1]Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021;80(1):31-35. doi:10.1136/annrheumdis-2020-217344. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.